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Biomedical subjects

M Okuyama

Publications and source records attributed to M Okuyama.

At least 37 records · Page 2Linked to original sources

A clinical study of surgical treatment of patients with carcinoma of the cervical esophagus extending to the thoracic esophagus.

OBJECTIVE: We studied optimum surgery for carcinoma of the cervical esophagus extending to the thoracic esophagus (Ce-Ut carcinoma). METHODS: Subjects were 13 patients diagnosed with Ce-Ut carcinoma treated at our institute from January 1989 to December 1998. Clinicopathologic information such as surgical procedures, pathologic findings, and postoperative complications were analyzed. RESULTS: In 10, laryngoesophagectomy was conducted due to tracheal invasion by the tumor. In 7, mediastinal tracheostomy was done because of the extended resection of the proximal trachea. In 3, the larynx was preserved and, in 2, cricopharyngeal myotomy was added. Lymph node metastasis was found only in the neck and the upper mediastinum at surgery and recurrences were all lung metastasis. The incidence of postoperative complications was very high (76.9%), and 1 patient died due to widespread tracheal necrosis. The cumulative 5-year survival rate for the group was 33.3% and that for the 9 curative cases was 50%, but most of the cases who underwent noncurative resection and/or who received preoperative therapy for widespread invasion to surrounding organs died within a year. CONCLUSION: The prognosis of patients who undergoing curative extended resection of the proximal trachea and suitable lymph node dissection in the neck and upper mediastinum may improve, and larynx-preserving surgery is recommended for patients without tracheal invasion. Despite preoperative chemoradiotherapy, the prognosis of patients with widespread invasion to surrounding organs was very poor, and clinical studies on new therapeutic strategies for these advanced cases are needed to improve the prognosis of Ce-Ut carcinoma patients.

Adult↗

Does central venous pressure reflect the circulating blood volume for the decrement of compliance just after esophagectomy?

This study investigates whether the pressure parameters obtained from the Swan-Ganz catheter (SGC) accurately reflect the circulating blood volume just after en bloc resection of the thoracic esophagus with regional lymph node dissection. It is well known that this operation induces severe hemodynamic changes and although the pressure parameters obtained from the SGC are an accepted means of monitoring circulating blood volume, we have often experienced a discrepancy between the SGC data and the clinical state. We examined the pressure parameters and diameter of the inferior vena cava (IVC) and left ventricle (LV), and the central venous compliance using SGC and echocardiography in ten patients who underwent esophagectomy for esophageal cancer. The central venous pressure, pulmonary arterial mean pressure, and pulmonary artery wedged pressure were significantly increased just after the operation compared with the preoperative levels, while the diameters of the IVC and LV decreased just after the operation. The compliances of the IVC decreased significantly just after the operation. The hemodynamic shift to the third space after esophagectomy induces decrement of the compliances of IVC. As the CVP does not always reflect the circulating blood volume, measuring the diameter of the IVC using echocardiography is extremely useful for monitoring circulating blood volume just after esophagectomy.

Blood Volume↗

Nitric oxide enhances expression and shedding of tumor necrosis factor receptor I (p55) in endothelial cells.

The biological actions of tumor necrosis factor-alpha (TNF-alpha) are mediated by 2 distinct receptors, TNF-RI (p55) and TNF-RII (p75). The extracellular domains of both receptors are shed in soluble form (sTNF-RI and sTNF-RII). The soluble receptors are involved in regulating TNF-alpha activities and may have therapeutic potential as TNF-neutralizing agents. However, it remains unclear as to what kind of physiological molecule can regulate TNF receptors. Nitric oxide (NO) mediates a variety of biological and pathophysiological functions. We hypothesized that NO may modulate the expression and shedding of TNF-RI. An NO donor, diethylamine/NO complex (NOC 5), increased sTNF-RI in the supernatants of ECV304, a human umbilical vein cell line, in a dose-dependent manner. TNF-RI mRNA in these cells was upregulated by NOC 5. 8-Br-cGMP and peroxynitrate had no effect on sTNF-RI release. Genistein and herbimycin A, inhibitors of tyrosine kinase, inhibited sTNF-RI release. Herbimycin A inhibited the levels of TNF-RI mRNA enhanced by NOC 5, which downregulated the surface expression of TNF-RI, indicating that NO is also involved in the shedding process of TNF-RI. The shedding of TNF-RI was abolished by a synthetic inhibitor of matrix metalloproteinase, KB-R8301. In conclusion, NO enhanced the release of sTNF-RI from endothelial cells by a cGMP-independent mechanism. Dual pathways suggested for NO-induced sTNF-RI release include (1) enhanced expression of TNF-RI, at least partially, by a tyrosine kinase-dependent mechanism and (2) increased shedding of TNF-RI by a type of metalloproteinase.

8-Bromo Cyclic Adenosine Monophosphate↗

Dobutamine stress echocardiography for the diagnosis of myocardial viability: assessment of left ventricular systolic velocities in longitudinal axis by pulsed Doppler tissue imaging.

Dobutamine (DOB) stress two-dimensional echocardiography is an established method for the detection of viable myocardium, but conventional assessment of wall motion is subjective. We measured quantitatively the left ventricular systolic velocities along the longitudinal axis by pulsed Doppler tissue imaging (DTI). In 30 patients with previous myocardial infarction, pulsed DTI focused on the infarct area was performed from an apical two- or four-chamber view before and during DOB (10 microg/kg/min) stress one day before coronary angioplasty. We calculated peak systolic velocity (S), regional pre-ejection period (PEP, the time interval from the onset of QRS to the onset of systolic wave) and regional ejection time (ET). Left ventriculography was obtained before and 3 months after coronary angioplasty to assess regional wall motion. Improvement of abnormal wall motion was observed in 19 patients (group P) but not in 11 (group N). Group P had significantly larger S and smaller PEP/ET than group N during DOB stress, although there were no significant differences in these indices between the groups at baseline. As a consequence, group P had a significantly larger percent change in S and a smaller percent change in PEP/ET than group N (164+/-39 vs 117+/-20% and 88+/-17 vs 116+/-29%, respectively, p < 0.01). It is suggested that the quantitative measurement of longitudinal systolic velocities during DOB stress by DTI is useful for the precise assessment of myocardial viability.

Adult↗

[Accidental decrease in the air flow during air/oxygen sevoflurane anesthesia].

We describe our experience of an accidental decrease in the air flow during air/oxygen sevoflurane anesthesia. According to the malfunction of an air compressor system, dehydration of the compressed air was inadequate, and the wet air was delivered to the anesthesia machine. The moisture was formed at a flow control valve to cause a gradual decrease in the air flow. The low-pressure alarm did not work at that time, because the pressure of the air supply was normal. There are two types of medical air, one is produced from the ambient air by air compressor system and another is the synthetic air which is a mixture of oxygen and nitrogen. Although the synthetic air is always dry and clean, the former contains dust, bacteria, and moisture. There is a possibility that all of these particles cannot be excluded before use. Accordingly, we must check the air compressor system routinely when a source of the compressed air is used.

Air↗

A novel compound heterozygote (FAP ATTR Arg104His/ATTR Val30Met) with high serum transthyretin (TTR) and retinol binding protein (RBP) levels.

A 64-year-old Japanese male suffering from very slowly progressive amyloidosis was studied by immunohistopathologic, mass spectrometric, and molecular genetic methods. After confirming the immunoreactivity of transthyretin (TTR) in the amyloid deposits using an anti-TTR polyclonal antibody, matrix-assisted laser desorption ionization/time-of-flight-mass spectrometry (MALDI/TOF-MS) was employed to look for the presence of variant TTR(s) in the serum. Two variant forms of TTR, one with a molecular weight 32 Da greater and another with a molecular weight 19 Da less than that of normal TTR encoded by the two respective alleles, were detected in this patient. Direct sequence analysis confirmed the presence of a double substitution: one at codon 30 from GTG (Val) to ATG (Met) and the other at codon 104 from CGC (Arg) to CAC (His) in the two alleles. MALDI/TOF-MS of the parents of the proband revealed that his father was a heterozygote of ATTR Arg104His and his mother was a heterozygote of ATTR Val30Met. The total TTR and retinol binding protein (RBP) concentrations in the serum samples of the proband were very high compared with those of FAP ATTR Val30Met patients and control subjects. We report here a new compound heterozygote in the TTR gene with familial amyloidotic polyneuropathy (FAP).

Acetaldehyde↗

Participation of the liver in generation of a vigorous anti-donor response after inoculation of donor spleen cells.

BACKGROUND: There is a general agreement that a preferential accumulation of alloantigens within the liver could induce hyporesponsiveness to the inoculated antigens. Entrapment of antigens in the liver may evoke an unique immune response in the organ and play a key role in determination of the fate of the transplanted grafts. To understand the immune response in the liver after inoculation of allogeneic donor antigens, we examined the immune response to systemically inoculated alloantigen in rats whose sensitized liver was replaced with that of naive rats or in naive rats whose liver was replaced with that of sensitized rats. METHODS: Using implantation of syngeneic liver (alloantigen-accumulated/naive) in rats (naive/alloantigen-sensitized), we compared the immune responses to alloantigen between rats with hepatic/extrahepatic alloantigen at 24 hr after alloantigen inoculation. This was called sensitized-liver-grafted (SLG)/sensitized-liver-removed (SLR) treatment. The immune response to donor alloantigen in this model was evaluated by survival of skin or heart grafts, complement-dependent cytotoxicity (CDC) titer and delayed-type hypersensitivity (DTH) response. RESULTS: Compared with the mean survival time (MST) in donor spleen cell inoculated (DSI) rats (skin and heart, MST: 8.2+/-1.1 and 10.7+/-2.3 days), SLG rats rejected allografts in an accelerated fashion (skin and heart, MST: 5.5+/-0.5 and 4.2+/-0.8 days), associated with higher CDC titer and DTH response. In contrast, allograft survival was moderately prolonged in SLR (skin and heart, MST: 16.5+/-2.6 and 29.5+/-3.7 days) associated with suppressed CDC titer and DTH response. The survival of third-party allograft after SLG or SLR treatment (skin, MST: 9.3+/-1.5 or 9.7+/-0.6 days) indicated that immunological hyper/hyporesponsiveness was donor-specific. CONCLUSIONS: A strong anti-donor immune response was induced by the transfer of donor antigen-baring liver to naive rats 24 hr after alloantigen inoculation, whereas removal of the liver suppressed alloimmune response. Our results indicate that vigorous anti-alloimmune response occurred in the liver after systemic inoculation of donor spleen cells.

Adoptive Transfer↗

Pretreatment of crude pancreatic islets with mitomycin C prolongs graft survival time in xenogeneic rat-to-mouse model.

BACKGROUND: Rejection of pancreatic islet grafts is still a serious problem. We evaluated the effect of mitomycin C (MMC) on the survival of crude islets grafts after xenogeneic islet transplantation. METHODS: WS (RT1k) rat islets pretreated with various concentrations of MMC (0, 1, 3.2, 10, 32, 50, 100, 320, and 1,000 microg/ml) were transplanted into C57BL/6 mice with streptozotocin-induced diabetes. In vivo graft function was assessed by a daily measurement of nonfasting blood glucose concentration in each animal. We also examined the separate effect of MMC on purified islets and contaminants present in the crude islet preparation. RESULTS: MMC at doses of 10, 32, 50, and 100 microg/ml resulted in a significant prolongation of the mean graft survival time from a control of 12.4+/-2.5 days to 23+/-7.4, 17.5+/-5.4, 25.5+/-14.7, and 26.7+/-8.9 days, respectively. Deterioration of glucose metabolism was noted when the dose exceeded 32 microg/ml, whereas at 320 microg/ ml, MMC failed to restore normoglycemia. Prolongation of survival time of crude islets was the result of its effect on islets and contaminant components of the crude islet preparation. In vitro study showed that MMC treatment at a higher concentration than 10 microg/ml reduces the stimulatory as well as proliferative capacity of lymph node cells. CONCLUSIONS: Pretreatment of pancreatic islets with MMC at 10 microg/ml prolongs xenograft survival without deterioration of in vivo graft function. This novel treatment modality represents a new strategy for the modulation of immunity of islets and contaminants in crude islet preparations.

Animals↗

Microchimerism in thymus is associated with up-regulated T helper type 1 cytokine transcription during cardiac allograft rejection in rats.

BACKGROUND: Intrathymic microchimerism (MC) is thought to be responsible for inducing allograft tolerance. However, the role of MC in the thymus gland after transplantation, particularly in the rejection response, is unknown. We investigated serial changes in intrathymic cytokine production associated with MC and allograft rejection. METHODS: Donor-specific cell injection (DSI) and heterotopic heart transplantation (HTx) were performed in the fully allogeneic combination using DA rats (RT1a) as donors and WS rats (RT1k)as recipients. MC was checked by polymerase chain reaction (PCR) using a donor RT1.Bbeta domain 1 region sequence-specific primers. Reverse transcription (RT)-PCR analysis of cytokine (interleukin [IL]-2, interferon-gamma, IL-4, and IL-10) profiles of the thymus was performed in animals given DSI, HTx, or DSI/HTx. RESULTS: DSI alone resulted in an immediate development of MC, detected by PCR, in various organs including the thymus, spleen, liver, and blood, of most rats, lasting for over 2 months. However, DSI-induced MC selectively disappeared in the thymus on day 7 after grafting, several days before the rejection of cardiac allograft. RT-PCR analysis of cytokine profiles showed that the levels of Th1 (IL-2 and interferon-gamma) cytokines transcribed in the thymus were higher than in the spleen. MC reappeared in the thymus on day 21 after grafting, but was not associated with elevation of Th1 cytokine transcription when allograft was replaced by fibrosis. CONCLUSIONS: Intrathymic MC does not always confer unresponsiveness to alloantigen, but can be eliminated after anti-donor response.

Animals↗

Effect of some heavy metal ions on copper-induced metallothionein synthesis in the yeast Saccharomyces cerevisiae.

Copper-induced metallothionein (MT) synthesis in Saccharomyces cerevisiae was investigated in order to associate this exclusively with Cu2+ in vivo, when cultured in nutrient medium containing other heavy metal ions. Expression of the CUP1 promoter/lacZ fusion gene was inhibited by all heavy metal ions tested, especially Cd2+ and Mn2+. By adding Cd2+ and Mn2+ at 10 microM concentration, the beta-galactosidase activity decreased by about 80% and 50% of the maximum induction observed with 1 mM CuSO4, respectively. Furthermore, cell growth was markedly inhibited by combinations of 1 mM-Cu2+ and 1 microM-Cd2+. Therefore, the yeast S. cerevisiae could not rely on MT synthesis as one of the copper-resistance mechanisms, when grown in a Cd2+ environment. In contrast, the presence of Mn2+ in the nutrient medium showed alleviation rather than growth inhibition by high concentrations of Cu2+. The recovery from growth inhibition by Mn2+ was due to decreased Cu2+ accumulation. Inhibitory concentrations of Co2+, Ni2+ and Zn2+ on expression of the CUP1p/lacZ fusion gene were at least one order of magnitude higher than that of Cd2+ and Mn2+. These results are discussed in relation to Cu2+ transport and Cu-induced MT synthesis in the copper-resistance mechanism of the yeast S. cerevisiae.

Cadmium↗

Outgrowth of pseudopodial cables induced by all-trans retinoic acid in micromere-derived cells isolated from sea urchin embryos.

Cultured cells derived from micromeres of sea urchin embryos underwent pseudopodial cable growth without spicule rod formation in the presence of all-trans retinoic acid (tRA) or insulin. Pseudopodial cable growth caused by tRA or insulin was inhibited by genistein, a protein tyrosine kinase inhibitor. Phosphorylation of protein tyrosine residue was augmented in the cells treated with tRA or insulin and was inhibited by genistein. Probably, protein tyrosine kinase takes an indispensable part in signal transduction systems for tRA and insulin in these cells. In tRA-treated cells, augmentation of the phosphorylation of protein tyrosine residue was accompanied by an increase in the activity of protein tyrosine kinase and was inhibited by actinomycin D, inhibiting cable growth. Activation of this enzyme in tRA-treated cells probably depends on RNA synthesis. In insulin-treated cells, augmentation of tyrosine residue phosphorylation occurred without any appreciable change in this enzyme's activity and was hardly affected by actinomycin D. Phosphorylation of protein tyrosine residue seems to be activated by the binding of insulin to an insulin receptor. Pseudopodial cable growth in these cells treated with tRA or insulin was inhibited by wortmannin. Phosphatidylinositol 3 kinase probably participates in tRA and insulin signal transduction systems.

Animals↗

Factors responsible for the prolongation of school refusal.

Two hundred and one school refusers (< or =18 years old), excluding schizophrenia, were treated at the Department of Neuropsychiatry, Hirosaki University Hospital between April 1975 and March 1995. Of 56 cases of school refusal, 31 did not improve for more than 2 years (group P), and 25 cases had improved in the degree of school refusal and social impairment (group B). The remaining cases were excluded from the analysis for several reasons. There was no significant difference between groups B and P in age at the first psychiatric evaluation as well as the age of onset of school refusal. The duration from school absence to the first evaluation of group P was significantly longer than that of group B. The duration of school refusal significantly and positively correlated with the duration from school absence to the first evaluation. Introversion and nervousness prolonged the duration of school refusal. The non-presence of volition for school attendance, and a low frequency of school attendance during the 1 month prior to the first evaluation influenced the prolongation of school refusal. The 'duration from school absence to the first evaluation', the 'patient's character', the 'non-presence of volition for school attendance' and the 'frequency of school attendance' influenced the prolongation of school refusal. The introduction of treatment within 10 months of the onset of school refusal is an important factor in preventing the prolongation of the school refusal.

Absenteeism↗

Anti-inflammatory cytokine profile in human heart failure: behavior of interleukin-10 in association with tumor necrosis factor-alpha.

Proinflammatory cytokines, i.e., tumor necrosis factor-alpha (TNFalpha), participate in the development and the progression of congestive heart failure (CHF). On the other hand, an anti-inflammatory cytokine may neutralize the proinflammatory cytokines of CHF. Interleukin-10 (IL-10) is known to suppress the synthesis of proinflammatory cytokines. IL-10 and the IL-10 receptor system was investigated in comparison with the behavior of TNFalpha in 68 patients with various causes of CHF (mean age: 61 years) and in 31 normal subjects (61 years). The circulating IL-10 level was higher in CHF patients than in normal subjects (p<0.05). The TNFalpha level was higher in CHF patients than in control subjects (p<0.005). The ratio of IL-10 to TNFalpha tended to be higher in control subjects than in patients with CHF (p = 0.09). With lipopolysaccharide treatment, the release of IL-10 was more enhanced from mononuclear leukocyte of patients with CHF than from control subjects (p<0.05). The expression of the IL-10 receptor estimated by flow cytometry of mononuclear leukocytes was higher in the CHF patients than in the normal subjects. The IL-10/IL-10 receptor system was activated, at least partly, to downregulate an excess of TNFalpha in patients with advanced CHF. IL-10 may be an important inherent component of the cytokine network of CHF.

Adult↗

Soft X-ray photochemistry beamline at SPring-8.

Design and construction of a soft X-ray beamline at SPring-8 is reported. The beamline utilizes high-quality linearly polarized soft X-rays obtainable from a figure-8 undulator for the study of photophysical and photochemical processes of atoms, molecules and surfaces in the inner-shell excitation region. It consists of two experimental stations, a photochemistry station and a chemical vapour deposition (CVD) station. A high-resolution grating monochromator is installed at the photochemistry station, while the intense undispersed undulator radiation is used at the CVD station. Unique features of the experimental chambers and of the analysis and characterization systems are described along with those of the monochromator.

Journal Article↗

Enhanced expression and shedding of tumor necrosis factor (TNF) receptors from mononuclear leukocytes in human heart failure.

TNFalpha exerts its functions by engaging two receptors (TNF-RI and TNF-RII). The extracellular parts of the receptors are proteolytically shed to the soluble forms by a matrix metalloproteinase-like enzyme (sTNF-RI and sTNF-RII). The soluble TNF receptors can neutralize TNFalpha activities. Circulating levels of both sTNF-RI and sTNF-RII are elevated in patients with congestive heart failure (CHF). It remains unclear how a large amount of sTNF-RI and sTNF-RII is mobilized into the circulation. Mononuclear leukocytes were obtained from 14 controls and 21 patients with CHF. TNF-RII of the cells from CHF patients was upregulated in the cell-surface expression and mRNA transcripts. Besides enhanced shedding of TNF-RII on the cells from CHF patients with phorbol myristate acetate (PMA), sera from CHF induced shedding of TNF-RII on the cells from normal volunteers. Thus, the enhancement of both expression and shedding of TNF-RII may be related to increased circulating levels of the soluble TNF receptor in patients with CHF. The presence of CHF may affect the regulation of TNF receptors, which may modulate the responsiveness to TNFalpha in the tissues of patients with CHF.

Adult↗

Bopindolol: a slowly dissociating antagonist from the beta-adrenoceptors in guinea pig atria.

The dissociating and/or residual inhibitory effects of bopindolol from beta-adrenoceptors of atria strips pretreated with this drug which was then washed out with buffers on the responses to isoprenaline were determined and compared with those of propranolol, pindolol, atenolol, and the two active metabolites of bopindolol: 18-502 and 20-785. Low concentrations of bopindolol (10(-9) to 10(-8) mol/l) and the active metabolite 18-502 (10(-9) mol/l) produced rightward shifts of the concentration-response curves. On the other hand, high concentrations of bopindolol (10(-7) mol/l) and metabolite 18-502 (10(-8) and 10(-7) mol/l) produced a reduced maximum response by isoprenaline, suggesting that these nonparallel rightward shifts have pD2 values of 7.57 (bopindolol) and 7.67 (18-502), respectively, at 0 min after washout with buffers. Pindolol (10(-7) mol/l) and propranolol (10(-7) and 10(-8) mol/l) also produced a rightward shift of isoprenaline response curves, and these concentration-response curves in guinea pig atria strips pretreated with pindolol (10(-7) mol/l) and propranolol (10(-6) mol/l) recovered to control levels. Neither of these drugs, however, reduced the maximum response by isoprenaline. A high concentration (10(-5) mol/l) of atenolol was required for a rightward shift of the isoprenaline concentration-response curve, and this drug also did not reduce the maximum response. Thus, we conclude that bopindolol and metabolite 18-502 slowly dissociate and act as noncompetitive beta-antagonists rather than easily reversible beta-adrenoceptor antagonists.

Adrenergic beta-Agonists↗

Automatic static threshold perimetry is useful for estimating the effects of laser photocoagulation on diabetic maculopathy.

Focal photocoagulation was performed on 18 eyes in 18 diabetes patients; a visual acuity test, fluorescein angiography and automated static threshold perimetry by Octopus automated static perimetry (program 31) were conducted before and 1, 3 and 6 months after krypton laser photocoagulation. Central field sensitivity and total loss were measured by automated static threshold perimetry. Group A (13 eyes) had a total loss of less than 150 dB. In these subjects, mild fluorescein leakage was detected within the area of the vascular arcade. In group B (5 eyes) with a total loss of greater than 150 dB, diffuse fluorescein leakage was also detected outside the vascular arcade. The central field sensitivity was reduced in 2 eyes of group B. The total loss worsened in 8 eyes of group A (61.5%) and 5 eyes of group B (100%). Inspection of photographs gave the impression that the degree of fluorescein leakage and the area of the avascular zone on fluorescein angiography accorded with total loss, thus suggesting that total loss reflects visual functions better than visual acuity or central field sensitivity. Therefore, automated static threshold perimetry appears to be a useful method for estimating visual functions after photocoagulation in diabetic maculopathy patients.

Adult↗